Alzheimer's disease (AD) is marked by the progressive decline of cognitive functions in affected patients and neuropathological features include brain neuronal loss (See Jellinger, & K. A., Bancher, C. J Neural Trans Suppl 54,77-95 (1998)). The causes of sporadic forms of AD representing more than 90% of all cases are unknown. In the brain glutamate receptors mediate fast excitatory neurotransmission and excitotoxicity, a mechanism proposed at the origin of neuronal death in neurodegenerative disorders including AD (See Choi, D. W. Neuron 1,623-634 (1988)).
While there has been considerable research into the mechanisms underlying Alzheimer's disease, it is desirable to develop methods for determining if a subject is at increased risk of developing Alzheimer's disease, using new markers, alone or together with another already known marker or more. It is also desirable to find new ways to investigate and combat this disorder.
For these reasons, the inventors have investigated the polymorphic variations of the human glutamate (kainate) receptor 5 (GluR-5) gene localized on chromosome 21. A variable number of tetraplet repeats AGAT is present in an intronic region of this gene (Ref. GENBANK Accession Number AP000238) and can be assessed by gene sequencing (See Gregor, P. et al. Hum Genet 94, 565-570 (1994)).
The inventors have provided evidence that the total number of tetraplet repeats AGAT present in an intronic region of this gene is significant of the risk of developing Alzheimer's disease.